Vol 6 n° 4 - Mild Cognitive Impairment
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3 6 9 B a s i c   r e s e a r c h Copyright © 2004 LLS SAS.  All rights reserved www.dialogues-cns.org Mild cognitive impairment: animal models Giancarlo Pepeu, MD Mild cognitive impairment (MCI) is an aspect of cogni- tive aging that is considered to be a transitional state between normal aging and the dementia into which it may convert. Appropriate animal models are necessary in order to understand the pathogenic mechanisms of MCI and develop drugs for its treatment. In this review, we identify the features that should characterize an ani- mal  model  of  MCI,  namely  old  age,  subtle  memory impairment,   mild   neuropathological   changes,   and changes in the cholinergic system, and the age at which these features can be detected in laboratory animals. These features should occur in aging animals with nor- mal motor activity and feeding behavior. The animal models may be middle-aged rats and mice, rats with brain ischemia, transgenic mice overexpressing amyloid precursor protein and presenilin 1 (tested at an early stage),  or  aging  monkeys.  Memory  deficits  can  be detected by selecting appropriately difficult behavioral tasks,  and  the  deficits  can  be  associated  with  neu- ropathological  alterations.  The  reviewed  literature demonstrates that, under certain conditions, these ani- mal species can be considered to be MCI models, and that cognitive impairment in these models responds to drug treatment.   © 2004, LLS SAS Dialogues Clin Neurosci. 2004;6:369-377. n the basis of the descriptions presented else- where in this issue, it is clear that it is difficult to identify or develop an animal model reproducing most, if not all, the features of human mild cognitive impairment (MCI). To begin with, an animal cannot complain about mem- ory, and it is difficult to assess whether its daily life is affected.  However,  correspondence  between  animal models and human pathology is only partial in all neu- rodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease. Nevertheless, even if they only partially reproduce the disease, animal models are quite useful for at least two purposes: understanding the pathogenic  mechanisms  of  a  disease; and  testing  the activity of new drugs to assess their potential activity prior to clinical trials. General features of MCI animal models If the purpose is to understand pathogenic mechanisms, the animal model should mimic as closely as possible the symptoms, neuropathology, and mechanisms of the dis- ease. Conversely, if the purpose is to demonstrate the potential efficacy of a drug, the animal model could be less complex, but should be easily available in large quan- tities and reasonably priced. On the basis of the clinical description of MCI and other considerations,  the  ideal  features  of  an  MCI  animal model are listed in Table I.The number of these features actually present in the models may vary according to the animal species used. Cerebrovascular alterations should be present only in models reproducing MCI occurring in patients affected by cerebrovascular diseases.1 In attempting to identify MCI animal models, the prob- lem arises of how to distinguish them from AD animal models. This problem parallels the situation facing the clinician having to distinguish between MCI and the ini- O Keywords: aging  rat;  aging mouse;  aging  monkey;  transgenic  mouse;  agedependent memory deficit Author  affiliations:   Department  of  Pharmacology,  
University  of  Florence, Italy Address for correspondence: Giancarlo Pepeu, MD, Professor of Pharmacology, Department of Pharmacology, University of Florence, Viale Pieraccini, 6, 50121 Florence, Italy (e-mail: giancarlo.pepeu@unifi.it)